Water → HCID 68706179, compound

HRID 218131Notes

Reaction equation

HRID 218131 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C@H:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:11]([CH3:15])([CH3:14])[C:12]#[N:13])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[CH3:22][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI.O>C1COCC1>[CH3:14][C:11]([CH3:15])([C@H:10]([C:6]1[CH:5]=[C:4]2[C:9](=[CH:8][CH:7]=1)[N:1]([CH3:22])[N:2]=[CH:3]2)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:12]#[N:13]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59251087HCID 59251087, compound

Product 1

HCID 68706179HCID 68706179, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of (S)-3-(1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanenitrile (80 mg, 0.29 mmol) in anhydrous THF (5 mL) was added 1.0M NaHMDS in THF (0.30 mL, 0.30 mmol) at RT under nitrogen. After stirring at RT for 10 min, methyl iodide (0.03 mL, 0.48 mmol) was added, and the reaction was stirred overnight. The reaction mixture was poured into water, extracted with ethyl acetate (2×100 mL), dried (MgSO4) and concentrated. The resulting N1 and N2 adducts were separated by HPLC to give 54 mg (62% yield) of the desired N1 adduct (S)-2,2-dimethyl-3-(1-methyl-1H-indazol-5-yl)-3-phenylpropanenitrile. MS found: (M+H)+=290.

Workup

  1. stirringthe reaction was stirred overnight
  2. extractionextracted with ethyl acetate (2×100 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe resulting N1 and N2 adducts were separated by HPLC

Sources & evidence

ORD record
ord-56805a7070e149d1843c92e7e6ca54d8
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

Loading…